Although protein-based therapeutics (e.g., monoclonal antibodies) are the fastest growing sector of the pharmaceutical industry, production costs remain incredibly high, and rapid commercialization of new protein drug candidates is not being widely realized. Both of these problems are due in part to the physical and chemical instabilities of proteins. Protein aggregation is arguably the most common and troubling manifestation of protein instability, occurring in almost all phases of development. Protein aggregates are usually normative in structure, may exhibit reduced biological activity, and can remain soluble or precipitate from solution. In addition to reducing the efficacy of a protein therapeutic, if administered to a patient aggregates can cause adverse reactions, such as immune response, sensitization, or even anaphylactic shock. To make the problem worse, for the practical application of traditional and novel drug delivery techniques protein-based therapeutics must be formulated at relatively high concentrations and preferentially remain stable for extended periods of time. The current approach toward stabilizing protein drugs against aggregation is trial-and-error testing of different combinations of cosolutes (e.g., salts, sugars, surfactants, amino acids) using empirically derived heuristics. While common, this approach is inefficient and does not always enable the discovery of stable protein solution formulations. Thus, many products must be lyophilized and reconstituted prior to injection, which is highly undesirable.
Due to the issues and complications associated with protein aggregation and the ineffectiveness of current stabilization methodologies, there is great interest in developing new solution additives that are effective at reducing or eliminating protein aggregation and are also effective at low concentrations.